Is PPRC1 p.Ser453Pro (c.1357T>C) pathogenic?

PPRC1 p.Ser453Pro (c.1357T>C) is classified Uncertain significance in PPRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.141); Absent from gnomAD v4.1.

How common is PPRC1 p.Ser453Pro (c.1357T>C) in the general population?

PPRC1 p.Ser453Pro (c.1357T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPRC1 p.Ser453Pro (c.1357T>C)?

AlphaMissense predicts likely benign (score 0.141) — an in-silico prediction, not a clinical call.

PPRC1 p.Ser453Pro

c.1357T>C · VCV4143429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.141 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.141	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP 0.87, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.94 · regional, not allelic
Overall
CADD	17.37	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPRC1
Protein: p.Ser453Pro
Coding: c.1357T>C
MANE Select: NM_015062
Type: single nucleotide variant
Location: chr10:102139865 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 42.49
Residue 453: the 'necessary for interaction with creb1 and nrf1 and for transcriptional coactivation' region; the 'disordered' region

Full PPRC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPRC1 p.Arg1428His Uncertain significance ★★ ⚠ same type
PPRC1 c.4551-5G>A Benign/Likely benign ★★ same type
PPRC1 p.Ala1005Val Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1134Val Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1192Val Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1243Val Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1258Thr Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1371Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pprc1-p-ser453pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown